敲减LncRNA TPT1-AS1抑制肝癌细胞侵袭及迁移  

Knockdown of long non-coding RNA TPT1-AS1 inhibits invasion and migration of hepatocarcinoma cells

作　　者：刘清秀 汪晓梅 吕娇健[1] 卢毅 赵园 樊晓鹏 Qing-Xiu Liu;Xiao-Mei Wang;Jiao-Jian Lv;Yi Lu;Yuan Zhao;Xiao-Peng Fan(Department of Hepatology and Infection,Lishui City People’s Hospital,Lishui 323000,Zhejiang Province,China;Department of Hepatopancreatobiliary Surgery,Lishui City People’s Hospital,Lishui 323000,Zhejiang Province,China)

机构地区：[1]丽水市人民医院肝科感染科,浙江省丽水市323000 [2]丽水市人民医院肝胆胰外科,浙江省丽水市323000

出　　处：《世界华人消化杂志》2021年第7期340-346,共7页World Chinese Journal of Digestology

摘　　要：背景长链非编码RNA(long non-coding RNA,lncRNA)肿瘤蛋白翻译调节因子1-反义RNA1(tumor protein translationally controlled regulator 1-antisence RNA 1,TPT1-AS1)TPT1-AS1可通过不同的作用方式影响肿瘤的侵袭转移,但其在肝癌中的具体作用和相关作用机制还有待进一步的实验验证.目的探讨lncRNA TPT1-AS1在肝癌中的表达及其对肝癌细胞侵袭迁移能力的影响.方法实时荧光定量PCR检测肝癌组织及肝癌细胞系(Huh7、SMMC-7721、HCCLM3和HepG2)中lncRNA TPT1-AS1的表达.靶向TPT1-AS1的小分子干扰RNA(siRNA targeted for TPT1-AS1,si-TPT1-AS1)转染后,经Transwell实验和划痕实验检测HepG2细胞侵袭及迁移能力的变化;Western blot评估上皮-间充质转分化进程(epithelial-mesenchymal transition,EMT)以及磷酸肌醇3激酶(phosphotylinosital 3 kinase,PI3K)/蛋白激酶B(protein kinase B,PKB/AKT)信号通路的活性.结果肝癌组织及肝癌细胞系(Huh7、SMMC-7721、HCCLM3和HepG2)中均可检测到lncRNA TPT1-AS1的高表达.转染siRNA-TPT1-AS1可抑制肝癌细胞HepG2的侵袭及迁移,同时抑制HepG2细胞的EMT进程.此外,下调lncRNA TPT1-AS1可抑制MMP-9的表达及PI3K/AKT信号通路的活性.结论LncRNA TPT1-AS1在肝癌中高表达.敲减lncRNA TPT1-AS1可抑制肝癌细胞HepG2的侵袭迁移,其作用机制可能与下调PI3K/AKT信号通路的活性以及下游基质金属蛋白酶9(matrix metalloproteinase 9,MMP-9)的表达,进而抑制细胞的EMT进程有关.BACKGROUND The long non-coding RNA(lncRNA)TPT1-AS1 has been proved to affect the migration and invasion of tumor cells by different means,but its specific role and related mechanisms in hepatic carcinoma still need further research.AIM To investigate the expression of TPT1-AS1 in hepatocarcinoma tissues and cell lines and explore its biological role in the invasion and migration of hepatocarcinoma cells.METHODS Real-time quantitative PCR was used to measure lncRNA TPT1-AS1 expression in hepatocarcinoma tissue and cell lines(Huh7,SMMC-7721,HCCLM3,and HepG2).After being transfected with small interfering RNA(siRNATPT1-AS1),the invasion and migration of HepG2 cells were detected by transwell assay and wound healing assay.Western blot was used to measure the epithelialmesenchymal transition(EMT)process and the activity of the PI3K/AKT pathway.RESULTS TPT1-AS1 was up-regulated in hepatopcarcinoma tissues and cell lines Huh7,SMMC-7721,HCCLM3,and HepG2.Transfection with siRNA-TPT1-AS1 noticeably restrained HepG2 cell invasion and migration,and suppressed the EMT process.Furthermore,TPT1-AS1 knockdown reduced MMP-9 expression and inhibited the activation of the PI3K/AKT pathway.CONCLUSION TPT1-AS1 is up-n regulated in hepatic carcinoma.Knockdown of TPT1-AS1 inhibits the invasion and migration of HepG2 cells via mechanisms that may be associated with reducing the activity of PI3K/AKT pathway and the expression of its downstream gene MMP-9,and inhibiting the EMT process.

关 键 词：lncRNA TPT1-AS1 肝癌 侵袭 迁移 PI3K/AKT 

分 类 号：R735.7[医药卫生—肿瘤]